The proposed investigations extend the applicant's research program directed at elucidating the etiology of substance use disorder (SUD). Utilizing almost 25 years of already collected longitudinal data and data to be collected during the next several years in this ongoing NIDA-funded Center for Education and Drug Abuse Research (CEDAR), analyses will be directed at joining individual vulnerability (particularly neurobehavior disinhibition, ND) and multiple facets of the environment to model the pathway(s) to SUD between ages 10-25. Neurobehavior disinhibition (encompassing the cognitive, affect and behavior components of psychological dysregulation) has been shown in 12 published reports I: i) have excellent psychometric properties (including predictive validity); ii) be informative for modeling SUD etiology in a developmental framework; iii) define a very high risk subset of 10-12 year olds having .95 probability of developing SUD; iv) correlate with electrophysiological and neuroimaging variables reflecting prefrontal cortex dysfunction; and, v) mediate adverse family, peer and neighborhood influences on SUD risk. This award will enable me to reallocate many of my day-to-day responsibilities while retaining leadership as the Center's PI. This award will provide me protected time for research integrating over two decades of accrued data for comprehensive analysis. This research is thematically guided, empirically grounded, and innovative in at least five ways: i) it captures SUD vulnerability integrating cognition, emotion, and behavior; ii) it integratively incorporates diverse age- appropriate environment influences; ii) it provides the opportunity to determine if there is differential salience of the various component of individual vulnerability and environment across the main age span of SUD development; iv) it is the first attempt to determine whether a composite index depicting a specific environtype at each age predisposes to SUD; and, v) employs item response theory (IRT) methods to quantify SUD severity taking into account all current and lifetime comorbid patterns in a mathematically accurate fashion, thereby enabling delineation of the covariation between severity of ND vulnerability and severity of SUD outcome. The proposed research aligns with the applicant's efforts in science advocacy pertaining to SUD etiology and prevention. By developing gender, ethnicity and age-appropriate algorithms for quantifying risk for SUD at the individual level withi a developmental framework, the NIH Roadmap framework will be advanced. Specifically, prevention can be designed that is empirically connected to the person's vulnerability and environment contexts. Hence, as a founding member of the Society of Prevention Research (SPR) and a member on the Board of the International Network of Patient-Centered Medicine (INPCM), a long-term career goal is to apply empirical research on SUD etiology for prevention practice.